The role of perfusion imaging in the management of acute ischemic stroke (AIS) is to establish the degree and extent of reduced regional cerebral blood flow (CBF), and to contribute to the identification of the ischemic penumbra - regions of hypoperfusion that may be salvaged by thrombolytic and/or endovascular recanalization therapies. Dynamic susceptibility contrast enhanced (DSC) techniques have been the main MR perfusion imaging method used in AIS. The initial DEFUSE cohort study suggested that perfusion-diffusion mismatch may predict clinical responses to thrombolytic therapy. Randomized trials (e.g. EPITHET, DIAS), however, have yielded ambiguous findings showing only trends to benefit when using perfusion and diffusion mismatch as a patient selection criterion for thrombolysis. To date, the value for identifying the ischemic penumbra in the management of AIS remains less than firmly established. Arterial spin labeled (ASL) perfusion MRI is an emerging non-contrast MRI method to measure CBF. With the latest implementation using pseudo- continuous ASL (pCASL) and background suppressed 3D GRASE, we recently demonstrated that ASL can be reliably applied for acute stroke imaging, and provides consistent results with DSC perfusion MRI for delineating hypoperfused brain regions. ASL also demonstrates the potential to illustrate collateral blood supply through delayed arterial transit effects as well as the use of vessel-selective ASL. Because ASL is easy, fast and does not require the injection of contrast agents, serial perfusion imaging can be performed to trace the dynamics of reperfusion and correlate with clinical outcomes. The main purpose of this proposal is to further develop, refine and evaluate the clinical utility of ASL for perfusion imaging in AIS In Aim 1, we will improve ASL perfusion quantification by including arterial transit time (ATT) measurement and perform a systematic evaluation of ASL and DSC perfusion MRI. In Aim 2, we will evaluate the utility of multi-delay ASL and vessel encoded pCASL in determining the state of collateral perfusion in AIS by comparison with the gold standard of digital subtraction angiography. In Aim 3, we will evaluate the clinical utility of serial ASL perfusion imaging by correlating with clinical outcomes such as reperfusion, hemorrhagic transformation (HT) and DSC measures of blood-brain barrier (BBB) permeability in AIS patients. We hypothesize that ASL hyperperfusion is associated with reperfusion, BBB leakage and is a predictor of HT in AIS patients. The present project capitalizes on the extremely rich clinical resources for AIS neuroimaging and treatments at UCLA. It is a translational project with the goal to develop and validate an entirely noninvasive and quantitative MRI method for routine clinical evaluation of AIS as well as other cerebrovascular disorders. PUBLIC HEALTH RELEVANCE: Stroke is the fourth leading cause of death in the US with more than 137,000 people dying each year from stroke. This project will develop, refine and validate a noninvasive and quantitative MRI method to measure cerebral blood flow in acute stroke patients, and is expected to improve the management and treatment of stroke patients.